H. Sawada et al., EFFICIENT PRODUCTION OF ANTI-(HEPATITIS-B VIRUS) ANTIBODIES AND THEIRNEUTRALIZING ACTIVITY IN CHIMPANZEES, Applied microbiology and biotechnology, 43(3), 1995, pp. 445-451
For industrial production of human monoclonal antibodies (hmAb) agains
t hepatitis B virus surface antigen (HBsAg), we scaled-up a short-term
perfusion culture in serum-free medium, which was chosen as the most
suitable culture method, to a 50-1 fermenter equipped with a rotating
shear filter. Using hydrophobic chromatography as the initial step of
hmAb purification, the mAb HBW4, HBW6 and W471 were isolated in good q
uality from the respective culture broths in yields of approximately 7
5%. Each of the three purified hmAb alone, and a cocktail of the three
, protected chimpanzees against HB virus, when injected intravenously
3 h after viral challenge, as long as the serum antibody levels were s
ignificant. A pharmacokinetic study using cynomolgus monkeys demonstra
ted that the hmAb have a long plasma half-life and bioavailability of
approximately 76% upon intramuscular injection in primates. Thus, anti
-HBsAg hmAb produced by an industrial process are expected to be succe
ssfully used in clinical fields.